guanfacine

Therapeutic Classification: antihypertensives, agents for attention deficit disorder

Pharmacologic Classification: alpha adrenergic agonists

BEERS REMS

Hypertension (in combination with thiazide-type diuretics) (immediate-release).
Attention-deficit hyperactivity disorder (ADHD) (as monotherapy or as adjunctive therapy to stimulants) (extended-release).

Stimulates CNS alpha₂-adrenergic receptors, producing a decrease in sympathetic outflow to heart, kidneys, and blood vessels. Result is decreased BP and peripheral resistance, a slight decrease in heart rate, and no change in cardiac output. Mechanism of action in ADHD is unknown.

Therapeutic effects:

Lowering of BP in hypertension.
Increased attention span in ADHD.

Absorption: Immediate-release is well absorbed (80%); extended-release has lower rate and extent of absorption (↑ absorption with high-fat meals).

Distribution: Appears to be widely distributed.

Metabolism/Excretion: 50% metabolized by the liver, 50% excreted unchanged by the kidneys.

Half-Life: 17 hr.

(antihypertensive effect)

ROUTE	ONSET	PEAK	DURATION
PO (single dose)	unknown	8–12 hr	24 hr
PO (multiple doses)	within 1 wk	1–3 mo	unknown

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

Severe coronary artery disease or recent MI;
Cerebrovascular disease;
Severe renal impairment;
Severe hepatic impairment;
History of hypotension, heart block, bradycardia, or cardiovascular disease;
OB: Other agents preferred for treatment of hypertension or ADHD in pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children 6 yr (safety and effectiveness not established);
Geri: Appears on Beers list. risk of CNS effects, orthostatic hypotension, and bradycardia in older adults. Avoid use for treatment of hypertension in older adults.

CV: bradycardia, chest pain, hypotension, palpitations, rebound hypertension, syncope

EENT: tinnitus

GI: constipation, dry mouth, abdominal pain, nausea

GU: erectile dysfunction

Neuro: drowsiness, headache, weakness, depression, dizziness, fatigue, insomnia, irritability

Resp: dyspnea

Drug-drug:

↑hypotension with other antihypertensives, nitrates, and acute ingestion of alcohol.
↑CNS depression may occur with other CNS depressants, including alcohol, antihistamines, opioid analgesics, tricyclicantidepressants, and sedative/hypnotics.
NSAIDs may ↓ effectiveness.
Adrenergics may ↓ effectiveness.
↑risk of hypotension and bradycardia with strong and moderate CYP3A4 inhibitors, including ketoconazole and fluconazole (↓ in dose of guanfacine may be needed).
Strong and moderate CYP3A4 inducers, including rifampin, efavirenz, and carbamazepine may ↓ effects (an ↑ in dose of guanfacine may be needed).
May ↑ levels of valproic acid.

Immediate-release and extended-release tablets should not be interchanged

Hypertension

PO (Adults ): Immediate-release: 1 mg once daily given at bedtime, may be ↑ if necessary at 3–4 wk intervals up to 2 mg/day; may also be given in 2 divided doses.

ADHD

PO (Adults and Children ≥6 yr): Extended-release: 1 mg once daily in morning or evening; may be ↑ by 1 mg/day at weekly intervals to achieve dose of 1–4 mg/day (6–12 yr) or 1–7 mg-day (13–17 yr) when used as monotherapy or 1–4 mg/day when used as adjunctive therapy. Concurrent strong or moderate CYP3A4 inhibitor:↓ initial and maintenance dose by 50%; Concurrent strong or moderate CYP3A4 inducer: Consider ↑ initial and maintenance dose up to double the recommended level (maintenance dose can be ↑ over period of 1–2 wk)

(Generic available)

Immediate-release tablets: 1 mg; 2 mg
Extended-release tablets (Intuniv): 1 mg; 2 mg; 3 mg; 4 mg

Hypertension: Monitor BP (lying and standing) and pulse frequently during initial dose adjustment and periodically during therapy. Report significant changes.
- Monitor frequency of prescription refills to determine adherence.
ADHD: Assess attention span, impulse control, and interactions with others.
Monitor BP and heart rate prior to starting therapy, following dose increases, and periodically during therapy. May cause hypotension, orthostatic hypotension, and bradycardia.

Lab Test Considerations:

May cause temporary, clinically insignificant ↑ in plasma growth hormone levels.
- May cause ↓ in urinary catecholamines and vanillylmandelic acid levels.

Do not confuse guanfacine with guaifenesin. Do not confuse Intuniv with Invega.
Do not substitute extended-release tablets for immediate-release tablets on a mg-mg basis. Doses are not the same.
PO: For hypertension: Administer daily dose at bedtime to minimize daytime sedation.
- For ADHD: Administer once daily in the morning or evening. DNC: Swallow extended-release tablets whole; do not crush, break, or chew. Do not administer with high fat meals, due to increased exposure.

Instruct patient/caregiver to take guanfacine as directed. Advise patient and parents to read the Medication Guide prior to starting therapy and with each Rx refill in case of changes. Instruct patients/caregivers not to discontinue guanfacine without consulting health care provider. Monitor blood pressure and pulse when reducing dose or discontinuing the drug. Taper the daily dose in decrements of no >1 mg every 3 to 7 days to minimize risk of rebound hypertension. If two or more doses are missed, may need to decrease dose and titrate to usual dose.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially cough, cold, or allergy remedies.
Caution patient to avoid alcohol and other CNS depressants, including opioids, while taking guanfacine.
Advise patient to notify healthcare professional if dry mouth or constipation persists. Frequent mouth rinses, good oral hygiene, and sugarless gum or candy may minimize dry mouth. Increase in fluid and fiber intake and exercise may decrease constipation.
Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
Advise patient to notify health care professional if dizziness, prolonged drowsiness, fatigue, weakness, depression, headache, sexual dysfunction, mental depression, or sleep pattern disturbance occurs. Discontinuation may be required if drug-related mental depression occurs.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Monitor breastfed infants exposed to guanfacine through breast milk for sedation, lethargy, and poor feeding. Inform patient about pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388.
Emphasize the importance of follow-up exams to evaluate effectiveness of medication.
Hypertension: Emphasize the importance of continuing to take medication as directed, even if feeling well. Medication controls but does not cure hypertension. Instruct patient to take medication at the same time each day. Take missed doses as soon as remembered; do not double doses. If 2 or more doses are missed, consult health care professional. Do not discontinue abruptly; may cause sympathetic overstimulation (nervousness, anxiety, rebound hypertension, chest pain, tachycardia, increased salivation, nausea, trembling, stomach cramps, sweating, difficulty sleeping). These effects may occur 2–7 days after discontinuation, although rebound hypertension is rare and more likely to occur with high doses.
Advise patient to make sure enough medication is available for weekends, holidays, and vacations. A written prescription may be kept in wallet in case of emergency.
Encourage patient to comply with additional interventions for hypertension (weight reduction, low-sodium diet, smoking cessation, moderation of alcohol consumption, regular exercise, and stress management).
Instruct patient and family on proper technique for BP monitoring. Advise them to check BP at least weekly and to report significant changes.
May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
ADHD: Instruct patient to take medication as directed at the same time each day. Take missed doses as soon as possible, but should not take more than the total daily amount in any 24-hr period. Do not stop taking abruptly; discontinue gradually at no more than 1 mg every 3–7 days. Monitor heart rate and BP during discontinuation. Advise patient and parents to read the Medication Guide prior to starting therapy and with each Rx refill.
Inform patient that sharing this medication may be dangerous.
Pedi: Advise parents to notify school nurse of medication regimen.

Decrease in BP without excessive side effects.
Improved attention span and social interactions in ADHD. Re-evaluate use if used for >9 wk.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆